Nickel-catalyzed site-selective C3–H functionalization of quinolines with electrophilic reagents at room temperature

Abstract

Herein, we disclose a mild and versatile nickel-catalyzed method for exclusive C3-selective thioetherification, alkylation, arylation, acylation, and phosphorylation of quinolines with a variety of electrophiles. Unactivated quinolines can be functionalized without directing groups at room temperature. Control experiments indicated that quinolines underwent 1,4-addition with nickel hydride species generated from β-H elimination of alkyl nickel intermediates to produce 1,4-dihydroquinolines, which further went through subsequent nucleophilic attack to external electrophiles and oxidative aromatization to generate C3–H-functionalized products.